Development of novel in-vitro chemical tools to simulate gastro-intestinal and lung environments in order to evaluate bioaccessibility of contaminants

开发新型体​​外化学工具来模拟胃肠道和肺部环境，以评估污染物的生物可及性

• 批准号: RGPIN-2015-06337
• 负责人: Zagury, Gérald
• 金额: $ 1.6万
• 依托单位: École Polytechnique de Montréal
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=590996
• 关键词: Development; novel; vitro; chemical; tools

Children are regularly exposed to toxic substances such as polycyclic aromatic hydrocarbons (PAHs) and metals via multiple pathways, including contaminated soil ingestion and inhalation of airborne particulate matter (PM). In risk assessment studies conducted on contaminated sites, assuming that 100% of a toxic substance in ingested or inhaled material enters the bloodstream (bioavailable) may lead to unrealistically high risk estimates. On the contrary, using the fraction of an inhaled or ingested pollutant which is soluble in simulated gastrointestinal conditions or simulated lung fluids (bioaccessible), measured via cost effective in-vitro tests, can help environmental engineers and risk assessors to obtain more accurate risk estimates. Such a chemical approach entails, at the same time, a reduction in the use of animal testing which involves strong ethical, technical, and financial issues. In spite of recent progress in chemical bioavailability research applied to metal-contaminated soils, much work is needed to advance the scientific basis for incorporating PAH bioaccessibility testing into contaminated site-specific risk assessments. The objective of my research program is to develop novel and improved in-vitro tools for oral bioaccessibility assessment (ingestion and inhalation) of metals and PAHs in contaminated soils, airborne particulate matter and children’s consumer products. More precisely, my work will aim at investigating and challenging recently developed PAH in-vitro bioaccessibility tests (FOREShT and IVG) and at assessing the influence of synthetic lipid sinks on in-vitro chemical bioavailability results using a wide array of industrial PAH-contaminated soils. In the case of PAH-contaminated sites, the success of this research program will allow for reduced land clean-up costs, following the formulation of more accurate site-specific reclamation criteria. Moreover, this research program brings the prospect of implementing less intrusive and more sustainable remediation approaches. This innovative research program also aims at gaining knowledge on  bioaccessibility in simulated lung fluids of PAHs and metals associated with airborne PMs using Gamble’s solution and artificial lysosomal fluids. Finally, building on our recent and pioneer work on chemical bioavailability of metals in toys and low-cost jewelry, this research program will also focus on developing a much-needed, dynamic version of the IVG bioaccessibility test, to simulate prolonged exposure to ingested items. Overall, this program will enable the training of highly qualified environmental engineers (1 PDF, 3 PhD, 2 MSc, 6 undergraduates) who will able to advance knowledge and develop rigorous in-vitro tests, with a deep understanding of how these tools will (and should) be used by environmental engineers and scientists within the scope of site remediation and risk assessment.

儿童经常通过多种途径接触到有毒物质，如多环芳烃（PAHs）和金属，包括摄入受污染的土壤和吸入空气中的颗粒物。在对污染场地进行的风险评估研究中，假设摄入或吸入的物质中有毒物质100%进入血液（生物可利用性），可能导致不切实际的高风险估计。相反，通过具有成本效益的体外试验测量吸入或摄入污染物中可溶于模拟胃肠道状况或模拟肺液（生物可及性）的部分，可以帮助环境工程师和风险评估人员获得更准确的风险估计。与此同时，这种化学方法需要减少动物试验的使用，这涉及到强烈的伦理、技术和财务问题。尽管最近在金属污染土壤的化学生物可利用性研究方面取得了进展，但将多环芳烃生物可利用性测试纳入污染场地特定风险评估的科学基础还需要做大量工作。我的研究计划的目标是开发新的和改进的体外工具，用于口服生物可及性评估（摄入和吸入）的金属和多环芳烃污染土壤，空气中的颗粒物和儿童消费品。更准确地说，我的工作将致力于调查和挑战最近开发的多环芳烃体外生物可及性测试（FOREShT和IVG），并利用广泛的工业多环芳烃污染土壤评估合成脂汇对体外化学生物可及性结果的影响。就多环芳烃污染的场址而言，这项研究方案的成功将有助于在制定更准确的具体场址填海标准之后减少土地清理费用。此外，该研究项目带来了实施侵入性更低、更可持续的修复方法的前景。这项创新的研究项目还旨在利用甘布尔溶液和人工溶酶体液，获得与空气中pmms相关的多环芳烃和金属的模拟肺液的生物可及性知识。最后，基于我们最近在玩具和低成本珠宝中金属的化学生物利用度方面的开创性工作，本研究项目还将重点开发一种急需的动态IVG生物利用度测试，以模拟长期暴露于摄入物品中。总体而言，该计划将培养高素质的环境工程师（1名PDF， 3名博士，2名硕士，6名本科生），他们将能够推进知识和开发严格的体外测试，并深入了解环境工程师和科学家将如何（并且应该）在现场修复和风险评估范围内使用这些工具。